Project Summary/Abstract: Cancer Biology and Therapeutics The Cancer Biology and Therapeutics (CBT) Program brings together 37 faculty, representing 12 departments at Dartmouth?s Geisel School of Medicine (Geisel), its Guarini School of Graduate and Advanced Studies, and the Dartmouth-Hitchcock Medical Center (DH), with research interests relevant to three central CBT Program themes: 1) Cancer cell signaling and metabolism, 2) Cell cycle biology and genome stability, and 3) Chromatin biology and oncogenic transcription. The shared goals of the CBT Program are to: i) advance the understanding of the basic mechanisms that underlie cancer initiation, progression, and metastasis to support prevention, diagnosis and treatment of cancer; ii) identify and validate new pathways and molecular targets for effective therapeutic intervention; iii) facilitate bi-directional translation to develop and improve novel therapeutic and diagnostic strategies. Peer-reviewed cancer-related research direct cost support currently totals $7.0M, with NCI funding representing 25% ($1.8M) and total direct costs summing to $7.9M. Twenty (20) CBT Program Members currently have a total of 28 CCSG-defined R01-equivalent awards. Using the same definition of cancer-related direct costs in 2014 (i.e., excluding all indirects as well as training and administrative direct costs), peer-reviewed cancer-related research direct costs ($7.0M) are up 14% compared to the combination of Cancer Mechanisms and Molecular Therapeutics in 2014 ($6.1M). Since 2015, the CBT Program has 446 cancer-related publications, 22% (98) intra-programmatic, 24% (109) inter-programmatic, 52% (232) with investigators from other institutions, and 24% (97) in high impact journals (i.e., impact factor >8). Compared to the combination of Cancer Mechanisms and Molecular Therapeutics in 2014, intra- programmatic publications have increased, to 22% from 15%, along with inter-programmatic (to 24% from 21%) and high impact (to 24% from 22%) in the current reporting period. The CBT Program will continue to pursue the proposed Specific Aims through building and strengthening multidisciplinary collaborations between basic, translational, and clinical researchers, mentorship of junior faculty members to academic independence, and promotion of partnerships of clinicians and laboratory scientists to drive the development of investigator- initiated clinical studies.